12362 Pathophysiology From Oxidative Stress Effectively Monitored In A Pre-clinical Model Of Type 2 Diabetes (T2D) With Point-of-care Microscale Magnetic Resonance (µNMR)

Abstract Disclosure: A.T. Alves: ; Co-Founder. ; Self. ; LarmorBio. S.S. Thamarath: ; Co-Founder. ; Self. ; LarmorBio. S. Fjordside: Employee; Self; Novo Nordisk. S. Sassower, MS.EE: ; Co-Founder. ; Self. ; LarmorBio. J. Han: None. L. Bouchard: Advisory Board Member; Self; LarmorBio. R. Rohr, BS.EE: ; Co-Founder, CEO. ; Self. ; LarmorBio. A.P. Chambers: Employee; Self; Novo Nordisk. The declining age of onset of T2D is a vital factor influencing its prospective burden. An early manifestation of the disease leads to an extended duration, which amplifies and accelerates the risk of micro and macrovascular complications. Oxidative stress is a major driver in the pathogenesis of T2D. Early detection and prevention of oxidative stress overload can improve and potentially modify the long-term harmful outcomes of metabolic diseases, including chronic hyperglycaemia.A novel µNMR assay was developed to monitor oxidative stress from minimally invasive plasma samples at the point of care. This approach is highly sensitive to redox changes in the blood microenvironment, including increased ferric iron (Fe3+), protein oxidation, and lipid peroxidation[1]. We hypothesized that oxidative stress would increase significantly faster in the disease group, enabling disease progression monitoring throughout the study and near real-time subject risk stratification based on the core pathophysiology of the diabetic phenotype.This 15-week longitudinal study (6th - 21st week of age) quantified oxidative stress in db/db and db/+ mice (n = 15 per group), accompanied by HbA1c, blood glucose (BG), and body weight (BW). The assay detailed separation (P ≤ 0.01) between the db/db and db/+ mice from the onset of the diabetic phenotype of db/db at 10 weeks of age (mean HbA1c = 6.5%). The oxidative stress monitored continued to increase in the subsequent weeks, where the HbA1c of db/db mice reached maximum (mean HbA1c = 8.8%). The definition of good (HbA1c ≤ 8) and poor (HbA1c > 8) glycaemic control was defined where sub-stratification (P ≤ 0.05) was achieved. Furthermore, the assay highlights a positive correlation with BW (ρ+/db = 0.52, P ≤ 0.0001, ρdb/db = 0.57, P ≤ 0.0001). In the two groups of mice, a positive correlation of oxidative stress with HbA1c (ρ = 0.58, P ≤ 0.0001) and BG (ρ = 0.47, P ≤ 0.0001) was reported. During the 15-week study, the control db/+ group exhibited a 13% mean increase in oxidative stress. In contrast, the db/db group demonstrated a cumulative 20% increase. No